Oral immunization with bacteriophage MS2-L2 VLPs protects against oral and genital infection with multiple HPV types associated with head & neck cancers and cervical cancer

• Published in: Antiviral research Vol. 166; pp. 56 - 65
• Main Authors: Zhai, Lukai, Yadav, Rashi, Kunda, Nitesh K., Anderson, Dana, Bruckner, Elizabeth, Miller, Elliott K., Basu, Rupsa, Muttil, Pavan, Tumban, Ebenezer
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2019
• Subjects: Animals; Antibodies, Neutralizing; Antibodies, Viral - immunology; Bacteriophage MS2-L2 VLPs; Buccal immunization; Capsid Proteins - immunology; Cross Protection - immunology; Epitopes - immunology; Female; Gardasil-9; Head and Neck Neoplasms - etiology; Head and Neck Neoplasms - prevention & control; Head and Neck Neoplasms - virology; HPV vaccine; Humans; Immunization - methods; Levivirus - immunology; Mice; Mucosal adjuvants; Neutralization Tests; Oncogene Proteins, Viral - immunology; Papillomaviridae - immunology; Papillomavirus Infections - prevention & control; Papillomavirus Vaccines - immunology; Respiratory Tract Infections - prevention & control; Thermostable vaccine; Uterine Cervical Neoplasms - etiology; Uterine Cervical Neoplasms - prevention & control; Uterine Cervical Neoplasms - virology; Vaccination - methods; Vaccines, Virus-Like Particle - immunology; Gardasil-9; Buccal immunization; Mucosal adjuvants; Thermostable vaccine; HPV vaccine; Bacteriophage MS2-L2 VLPs
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2019.03.012

Human papillomaviruses (HPVs) are the most common sexually transmitted infections. HPVs are transmitted through anogenital sex or oral sex. Anogenital transmission/infection is associated with anogenital cancers and genital warts while oral transmission/infection is associated with head and neck cancers (HNCs) including recurrent respiratory papillomatosis. Current HPV vaccines protect against HPV types associated with ∼90% of cervical cancers and are expected to protect against a percentage of HNCs. However, only a few studies have assessed the efficacy of current vaccines against oral HPV infections. We had previously developed a mixed MS2-L2 candidate HPV vaccine based on bacteriophage MS2 virus-like particles (VLPs). The mixed MS2-L2 VLPs consisted of a mixture of two MS2-L2 VLPs displaying: i) a concatemer of L2 peptide (epitope 20–31) from HPV31 & L2 peptide (epitope 17–31) from HPV16 and ii) a consensus L2 peptide representing epitope 69–86. The mixed MS2-L2 VLPs neutralized/protected mice against six HPV types associated with ∼87% of cervical cancer. Here, we show that the mixed MS2-L2 VLPs can protect mice against additional HPV types; at the genital region, the VLPs protect against HPV53, 56, 11 and at the oral region, the VLPs protect against HPV16, 35, 39, 52, and 58. Thus, mixed MS2-L2 VLPs protect against eleven oncogenic HPV types associated with ∼95% of cervical cancer. The VLPs also have the potential to protect, orally, against the same oncogenic HPVs, associated with ∼99% of HNCs, including HPV11, which is associated with up to 32% of recurrent respiratory papillomatosis. Moreover, mixed MS2-L2 VLPs are thermostable at room temperature for up to 60 days after spray-freeze drying and they are protective against oral HPV infection. •Buccal immunization with mixed MS2-L2 VLPs in the presence of CT/MPLA elicits systemic IgG response.•Mixed MS2-L2 VLPs in the presence of CT/MPLA enhances oral and vaginal HPV protection following buccal immunization.•Mice immunized, buccally, with mixed MS2-L2 VLPs are protected against genital infection with four HPV types.•Buccal immunization with mixed MS2-L2 VLPs protects against oral infection with five oncogenic HPV types.•Spray-freeze dried VLPs, without CT/MPLA, are thermostable and are immunogenic after 60 days storage at room temperature.